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Heavy metals are ubiquitous environmental contaminants that are capable of inducing a broad range of physiological, biochemical and behavioural dysfunctions. Heavy metal poisoning remains a persistent public health problem in Malaysia and throughout the world. Exposure to toxic metals and compounds containing them through inhalation, ingestion or skin contact may cause various pathophysiological conditions, and the nervous system is the most susceptible organ system to this exposure causing a condition known as heavy metal-mediated neurotoxicity. This review summarises the current understanding of the mechanisms by which arsenic, lead and mercury induce heavy metal-mediated neurotoxicity. These heavy metals cause toxic manifestations in the nervous system primarily through the presence of excessive pro-oxidants and depletion of antioxidants, causing an imbalance homeostasis also described as oxidative stress. In addition, this article also reviews previous common chelation treatments and emerging antioxidant treatments since antioxidants have become the current interest in the prevention and treatment of these heavy metal-mediated toxicities. [ABSTRACT FROM AUTHOR]

Background and Objectives: This systematic review aimed to compare the effect of chitosan in smear layer removal with other commonly used chelators during root canal treatment. Materials and Methods: The PRISMA guidelines were followed. Ex vivo studies performed in non-endodontically treated extracted human permanent teeth with a fully formed apex, in which sodium hypochlorite was the main irrigant and chitosan was used as final irrigation to observe its capacity to remove the smear layer using a Scanning Electron Microscope (SEM), were included. In addition, reviews, letters, opinion articles, conference abstracts, book chapters, or articles that did not use a control group were excluded. A literature search was undertaken without limits on time or language, until February 2024, in PubMed—MEDLINE, Scopus, Web of Science, and in the electronic archives of four endodontic journals. The risk of bias was evaluated by adapting the risk of bias assessment used in a previous study. Study selection, data collection, and synthesis were performed and the risk of bias was assessed by two independent reviewers. Results: Six studies fulfilled the eligibility criteria and were included. Four studies found chitosan to be as effective as EDTA and one paper showed it was more effective than EDTA and MTAD; however, one article found it to be comparable to citric acid. The overall risk of bias was medium. Quantitative analysis of the results was not possible due to the heterogeneity found between the study methodologies of the included articles. Conclusions: Within the limitations of this study, 0.2% chitosan may be considered as a promising irrigation solution when employed as a final irrigant in order to remove the smear layer. Nonetheless, a standardized protocol for the use of chelators in root canal treatment should be established in future studies. [ABSTRACT FROM AUTHOR]

Phytoremediation is an environmentally friendly and highly promising method for soil remediation, with the core issue being the selection of suitable plants and applicable conditions. During the remediation of uranium-contaminated environments, the enrichment of uranium adversely affects the normal growth of plants, causing stress effects. This study aimed to explore the stress response mechanism of Bidens pilosa L. to uranium in the soil and the influence of chelating agents on its uranium enrichment capacity through experiments on the remediation of uranium-contaminated soil. The phenotypic, physiological, and chlorophyll fluorescence parameters of Bidens pilosa L., as well as its uranium enrichment capacity, were studied under the influence of chelating agents and uranium. The results show that with the increase of uranium concentration, the levels of soluble protein, malondialdehyde (MDA), peroxidase (POD), and catalase (CAT) in Bidens pilosa L. first increase and then decrease. The maximum quantum yield (Fv/Fm) and non-photochemical quenching coefficient (NPQ) significantly decrease with the increase of uranium concentration, while the actual quantum yield (ΦPSⅡ) gradually increases. The application of chelating agents significantly enhances the uranium enrichment capacity of Bidens pilosa L. Low concentrations of chelating agents promote the synthesis of soluble protein, POD, and CAT, and reduce MDA content. Additionally, low concentrations of chelating agents increase the Fv/Fm and ΦPSⅡ values of Bidens pilosa L. However, they could also affect the open center structure of PSⅡ in plants, leading to the damage of the photoprotection system. High concentrations of chelating agents could directly cause plant death. In terms of enrichment capacity, when the soil uranium concentration is 50 mg/kg, under the action of 20 mmol/kg oxalic acid, Bidens pilosa L. achieves a maximum total enrichment coefficient of 6.29, with an above-ground part enrichment coefficient of 4.26 and a transfer coefficient of 2.09, exceeding the lower limits defined for hyperaccumulator plants. Thus, it can be defined as a hyperaccumulator plant, but under these conditions, Bidens pilosa L. does not survive for more than 24 h. Therefore, if Bidens pilosa L. is used as a phytoremediation material for uranium-contaminated soil, the application of 10 mmol/kg citric acid can enhance its uranium enrichment capacity while ensuring better survival rates. The above results indicate that by adjusting the concentration of chelating agents, it is possible to effectively increase the uranium enrichment efficiency of Bidens pilosa L. while minimizing damage to the plant itself, thereby playing a more significant role in the remediation of uranium-contaminated soils. Furthermore, understanding the precise biochemical and physiological responses of Bidens pilosa L. to uranium stress and chelating agents can help in developing more refined strategies for using this plant in various contaminated environments. This deeper insight into the plant’s response mechanisms also opens up avenues for interventions to enhance its resilience and accumulation capacity, making phytoremediation a more viable and efficient option for large-scale environmental cleanup efforts.

Chelation is the rational treatment modality in metal overload conditions, but chelators are often non-selective and can, hence, cause an imbalance in the homeostasis of physiological metals including calcium and magnesium. The aim of this study was to develop an affordable, rapid but sensitive and precise method for determining the degree of chelation of calcium and magnesium ions and to employ this method for comparison on a panel of known metal chelators. Spectrophotometric method using o-cresolphthalein complexone (o-CC) was developed and its biological relevance was confirmed in human platelets by impedance aggregometry. The lowest detectable concentration of calcium and magnesium ions by o-CC was 2.5 μM and 2 μM, respectively. The indicator was stable for at least 110 days. Four and seven out of twenty-one chelators strongly chelated calcium and magnesium ions, respectively. Importantly, the chelation effect of clinically used chelators was not negligible. Structure–activity relationships for eight quinolin-8-ols showed improvements in chelation particularly in the cases of dihalogen substitution, and a negative linear relationship between pKa and magnesium chelation was observed. Calcium chelation led to inhibition of platelet aggregation in concentrations corresponding to the complex formation. A novel method for screening of efficacy and safety of calcium and magnesium ion chelation was developed and validated. [ABSTRACT FROM AUTHOR]

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Abstract Background Metal ions play vital roles in regulating various biological systems, making it essential to control the concentration of free metal ions in solutions during experimental procedures. Several software applications exist for estimating the concentration of free metals in the presence of chelators, with MaxChelator being the easily accessible choice in this domain. This work aimed at developing a Python version of the software with arbitrary precision calculations, extensive new features, and a user-friendly interface to calculate the free metal ions. Results We introduce the open-source PyChelator web application and the Python-based Google Colaboratory notebook, PyChelator Colab. Key features aim to improve the user experience of metal chelator calculations including input in smaller units, selection among stability constants, input of user-defined constants, and convenient download of all results in Excel format. These features were implemented in Python language by employing Google Colab, facilitating the incorporation of the calculator into other Python-based pipelines and inviting the contributions from the community of Python-using scientists for further enhancements. Arbitrary-precision arithmetic was employed by using the built-in Decimal module to obtain the most accurate results and to avoid rounding errors. No notable differences were observed compared to the results obtained from the PyChelator web application. However, comparison of different sources of stability constants showed substantial differences among them. Conclusions PyChelator is a user-friendly metal and chelator calculator that provides a platform for further development. It is provided as an interactive web application, freely available for use at https://amrutelab.github.io/PyChelator , and as a Python-based Google Colaboratory notebook at https://colab.research.google.com/github/AmruteLab/PyChelator/blob/main/PyChelator_Colab.ipynb .

In view of the high concentration of heavy metal in fly ash produced by a municipal solid waste incineration plant in Shenzhen, this paper based on the screening of various chelating agent components, and the response surface methodology was used to design the experiment. The effects of complex chelator on the chelation of Zn, Pb and Cd were evaluated by model fitting and variance analysis, and the chelating mechanism was analyzed by SEM, FTIR and XPS. The results showed that the combination of 2.5%(w) calcium superphosphate + 3%(w) sodium dimethyldithiocarbamate water agent, supplemented by 0.074%(w) sodium dodecyl benzene sulfonate, could achieve the best chelating effect and applicability for multiple batches of high concentration fly ash. Calcium superphosphate and sodium dimethyldithiocarbamate water agent had significant effects on the chelation of Zn and Cd, respectively, while Pb was affected by the antagonism of the two components. During the chelation and aging process, the components of heavy metals in the original ash were dissolved, crystallized and fixed: Zn was combined with phosphate, but aging at high temperature would reduce its chelating stability, Pb formed a stable compound with high valence, while Cd was mainly coated by the cross-linking group of organic chelating agent. [ABSTRACT FROM AUTHOR]

A new type of diborate clathrochelate (cage) ligand featuring nine inwardly pointing nitrogen donors that form a large, rigid cavity, termed a mausolate, is presented. The cavity size and high denticity make this an attractive delivery vehicle for large radionuclides in nuclear medicine. Metal mausolate complexes are stable to air and water (neutral pH) and display extremely high thermal stability (>400 °C). Lanthanide uptake by the mausolate ligand occurs rapidly in solution at room temperature and once complexed, the lanthanide ions are not displaced by a 250‐fold excess of a competitive lanthanide salt over more than one week. [ABSTRACT FROM AUTHOR]

Background: Metal ions play vital roles in regulating various biological systems, making it essential to control the concentration of free metal ions in solutions during experimental procedures. Several software applications exist for estimating the concentration of free metals in the presence of chelators, with MaxChelator being the easily accessible choice in this domain. This work aimed at developing a Python version of the software with arbitrary precision calculations, extensive new features, and a user-friendly interface to calculate the free metal ions. Results: We introduce the open-source PyChelator web application and the Python-based Google Colaboratory notebook, PyChelator Colab. Key features aim to improve the user experience of metal chelator calculations including input in smaller units, selection among stability constants, input of user-defined constants, and convenient download of all results in Excel format. These features were implemented in Python language by employing Google Colab, facilitating the incorporation of the calculator into other Python-based pipelines and inviting the contributions from the community of Python-using scientists for further enhancements. Arbitrary-precision arithmetic was employed by using the built-in Decimal module to obtain the most accurate results and to avoid rounding errors. No notable differences were observed compared to the results obtained from the PyChelator web application. However, comparison of different sources of stability constants showed substantial differences among them. Conclusions: PyChelator is a user-friendly metal and chelator calculator that provides a platform for further development. It is provided as an interactive web application, freely available for use at https://amrutelab.github.io/PyChelator, and as a Python-based Google Colaboratory notebook at https://colab.research.google.com/github/AmruteLab/PyChelator/blob/main/PyChelator_Colab.ipynb. [ABSTRACT FROM AUTHOR]

One of the challenges of agromining is the adoption of more environmentally‐friendly solutions to improve plant biomass yields and Ni concentrations in plants. Here, we focused on four sustainable solutions for optimizing nickel phytoextraction by the hyperaccumulator Odontarrhena chalcidica: a biostimulant, another biostimulant/plant defense stimulator, artificial root exudates, and a biodegradable metal chelator. Their effects on the growth and physiology of O. chalcidica, on Ni phytoextraction capacity, on physicochemical soil characteristics, and on the diversity of rhizosphere and endophytic bacteria were compared to a conventional mineral fertilizer. A 5‐month pot experiment was carried out with O. chalcidica growing on an ultramafic soil. Element concentrations in both soil and plant were measured. Moreover, numerous compounds were analyzed (photosynthetic pigments, malondialdehyde, flavonoids, free amino acids, and starch). We also characterized rhizosphere and endophytic bacterial communities associated with this hyperaccumulator. Biostimulants appeared to be a promising way of improving Ni concentration in shoots and plant biomass production, and showed a positive effect on bacterial richness and diversity. In contrast, our experiments did not show that artificial exudates and mineral fertilizer had a positive effect on Ni phytoextraction. Finally, the biodegradable chelator had no significant effect. The use of sustainable amendments into a Ni agromining system improved both plant biomass and Ni yields, in comparison to mineral fertilization. Thus, improving agromining by replacing mineral fertilizers would be an eco‐efficient strategy. [ABSTRACT FROM AUTHOR]

Objectives: Currently, premixed putty-type bioceramic cements (PPBCs) have become popular materials for root-end fillings. This study investigated three root-end filling techniques using PPBCs and calcium silicate-based sealers including EDTA pretreatment. Materials and methods: Ninety root segments were prepared and standardized with an artificial fin and lateral canal, and assigned to three groups (n = 30). Root-end fillings were placed using BC-RRM Putty alone (Group PA), injection of BC sealer followed by BC-RRM Putty (Lid Technique: Group LT) or BC-RRM Putty with BC sealer coating (Deep putty packing technique: Group DP). Half of each group was pretreated with 17% EDTA. The radiographic images of the specimens were assessed by five graders and push-out bond strength tests were conducted. The data were analyzed with a general linear model including two-way ANOVA and chi-square test at a significance level of 5%. Results: DP approach demonstrated significantly higher bond strength than LT (P < 0.05). However, there was no statistically significant difference in bond strength between PA and either DP or LT. EDTA pretreatment had no significant effect on push-out bond strength. Radiographically, for the main canal, PA and DP scored significantly higher than LT. In the fin, PA scored significantly higher than others (P < 0.05). Conclusion: Our study highlights variations in root-end filling techniques. Injecting a bulk of bioceramic sealer before the placement of PPBCs may reduce bond strength and radiopacity. The application of PPBCs alone or in the deep putty technique demonstrates potential for favorable outcomes. EDTA pretreatment did not enhance bond-strength. Clinical relevance: Careful selection and application of bioceramic materials and techniques in root-end fillings may influence the outcome of endodontic root-end surgery. When PPBCs and calcium silicate-based sealers are used together for root-end fillings, sealer followed by deep putty application may offer improved bond strength and radiographic fill compared to the lid technique. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a mosaic of neurodevelopmental conditions composed of early-onset social interaction and communication deficits, along with repetitive and/or restricted patterns of activities, behavior, and interests. ASD affects around 1% of children worldwide, with a male predominance. Energy, porphyrin, and neurotransmitter homeostasis are the key metabolic pathways affected by heavy metal exposure, potentially implicated in the pathogenesis of ASD. Exposure to heavy metals can lead to an altered porphyrin metabolism due to enzyme inhibition by heavy metals. Heavy metal exposure, inborn genetic susceptibility, and abnormal thiol and selenol metabolism may play a significant role in the urinary porphyrin profile anomalies observed in ASD. Altered porphyrin metabolism in ASD may also be associated with, vitamin B6 deficiency, hyperoxalemia, hyperhomocysteinemia, and hypomagnesemia. The present review considers the abnormal porphyrin metabolism in ASD in relation to the potential pathogenic mechanism and discusses the possible metabolic therapies such as vitamins, minerals, cofactors, and antioxidants that need to be explored in future research. Such targeted therapeutic therapies would bring about favorable outcomes such as improvements in core and co-occurring symptoms. [ABSTRACT FROM AUTHOR]

Abstract Fly ash derived from municipal solid waste incinerators (MSWIs) harbors significant quantities of heavy metals with high leaching toxicity, resulting in detrimental environmental effects. Pb2+ in fly ash is the ion most likely to exceed permissible levels. However, chemical stabilization methods demonstrate poor efficacy in stabilizing Pb2+ under acidic conditions. Herein, we have developed a robust acid-resistant chelating polymer (25DTF) for enhanced stabilization of Pb2+ in fly ash. 25DTF was synthesized through the reaction of formaldehyde with 2,5-dithiourea. 25DTF exhibited remarkable chelation efficiency, nearing 100%, for Pb2+ in fly ash. 25DTF demonstrated exceptional chelation efficiency, surpassing 99.9%, when interacting with Pb2+ in fly ash at pH ≤ 7. Even under acidic conditions, 25DTF effectively prevented the secondary dissolution of Pb2+. Additionally, it indicated outstanding Pb2+ chelation efficiency across diverse regions of China. The 25DTF chelating agent shows considerable potential in alleviating metal ion contamination in soil, wastewater, and urban environmental management, thereby fostering advancements in environmental stewardship.

Background and Objectives: This systematic review aimed to compare the effect of chitosan in smear layer removal with other commonly used chelators during root canal treatment. Materials and Methods: The PRISMA guidelines were followed. Ex vivo studies performed in non-endodontically treated extracted human permanent teeth with a fully formed apex, in which sodium hypochlorite was the main irrigant and chitosan was used as final irrigation to observe its capacity to remove the smear layer using a Scanning Electron Microscope (SEM), were included. In addition, reviews, letters, opinion articles, conference abstracts, book chapters, or articles that did not use a control group were excluded. A literature search was undertaken without limits on time or language, until February 2024, in PubMed—MEDLINE, Scopus, Web of Science, and in the electronic archives of four endodontic journals. The risk of bias was evaluated by adapting the risk of bias assessment used in a previous study. Study selection, data collection, and synthesis were performed and the risk of bias was assessed by two independent reviewers. Results: Six studies fulfilled the eligibility criteria and were included. Four studies found chitosan to be as effective as EDTA and one paper showed it was more effective than EDTA and MTAD; however, one article found it to be comparable to citric acid. The overall risk of bias was medium. Quantitative analysis of the results was not possible due to the heterogeneity found between the study methodologies of the included articles. Conclusions: Within the limitations of this study, 0.2% chitosan may be considered as a promising irrigation solution when employed as a final irrigant in order to remove the smear layer. Nonetheless, a standardized protocol for the use of chelators in root canal treatment should be established in future studies.

Fly ash derived from municipal solid waste incinerators (MSWIs) harbors significant quantities of heavy metals with high leaching toxicity, resulting in detrimental environmental effects. Pb2+ in fly ash is the ion most likely to exceed permissible levels. However, chemical stabilization methods demonstrate poor efficacy in stabilizing Pb2+ under acidic conditions. Herein, we have developed a robust acid-resistant chelating polymer (25DTF) for enhanced stabilization of Pb2+ in fly ash. 25DTF was synthesized through the reaction of formaldehyde with 2,5-dithiourea. 25DTF exhibited remarkable chelation efficiency, nearing 100%, for Pb2+ in fly ash. 25DTF demonstrated exceptional chelation efficiency, surpassing 99.9%, when interacting with Pb2+ in fly ash at pH ≤ 7. Even under acidic conditions, 25DTF effectively prevented the secondary dissolution of Pb2+. Additionally, it indicated outstanding Pb2+ chelation efficiency across diverse regions of China. The 25DTF chelating agent shows considerable potential in alleviating metal ion contamination in soil, wastewater, and urban environmental management, thereby fostering advancements in environmental stewardship. [ABSTRACT FROM AUTHOR]

Xanthomicrol (4′,5-dihydroxy-6,7,8-trimethoxyflavone) is the main active component of Dracocephalum kotschyi Boiss leaf extract. It has showed selective cytotoxic activity against some cancer cell lines and little effect on human fetal foreskin fibroblast cells used as nonmalignant control. This study aimed to develop 99mTc-labeled xanthomicrol and to evaluate its efficiency as a new tumor imaging agent. l,l-Ethylene dicysteine (EC) chelator was conjugated to xanthomicrol. EC-Xanthomicrol was labeled with technetium-99m by using tin chloride as a reducing agent and incubating at room temperature. Radiochemical purity and in vitro stability were analyzed by thin layer chromatography and high-performance liquid chromatography. In vitro cellular uptake and binding profile of radio-conjugate was determined on C6 glioma cells. In vivo bioevaluation and imaging studies of [99mTc]Tc-EC-Xanthomicrol were performed in C6 glioma tumor induced rat at different time points after injection of radio-conjugate. The high radiochemical yield (>95 %) was achieved for [99mTc]Tc-EC-Xanthomicrol which was stable up to 6 h. The radio-conjugate indicated high cell uptake (35.12 % at 2 h) which demonstrated to be specific. Tumor uptake was seen for [99mTc]Tc-EC-Xanthomicrol (1.23 ± 0.14 %ID/g) at 1 h post injection. Scintigraphy confirmed that tumors could be visualized clearly with [99mTc]Tc-EC-Xanthomicrol. The results indicated that [99mTc]Tc-EC-Xanthomicrol has potential to be considered as a new radiotracer in glioma tumor imaging. [ABSTRACT FROM AUTHOR]

Zinc is a ubiquitous contaminant in many buffers, purified products and common labware that has previously been suggested to impact on the results of functional GlyR studies and may inadvertently cause the effectiveness of some GlyR modulators to be over-estimated. This could greatly impact the assessment of potential drug-candidates and contribute to the reduced effectiveness of compounds that reach clinical stages. This is especially true for GlyR modulators being developed for pain therapeutics due to the changes in spinal zinc concentrations that have been observed during chronic pain conditions. In this study we use two-electrode voltage clamp electrophysiology to evaluate the metal chelators tricine and Ca-EDTA, and show that tricine produces inhibitory effects at GlyRα1 that are not mediated by zinc. We also utilized the zinc insensitive W170S mutation as a tool to validate metal chelators and confirm that zinc contamination has not impacted the examination of lipid modulators previously developed by our lab. This study helps to further develop methods to negate the impact of contaminating zinc in functional studies of GlyRs which should be incorporated into future studies that seek to characterize the activity of novel modulators at GlyRs.

The few commercially available chemosensors and published probes for in vitro Zn2+ detection in two-photon microscopy are compromised by their flawed spectroscopic properties, causing issues in selectivity or challenging multistep syntheses. Herein, we present the development of an effective small molecular GFP chromophore-based fluorescent chemosensor with a 2,2′-bipyridine chelator moiety (GFZnP BIPY) for Zn2+ detection that has straightforward synthesis and uncompromised properties. Detailed experimental characterizations of the free and the zinc-bound compounds within the physiologically relevant pH range are presented. Excellent photophysical characteristics are reported, including a 53-fold fluorescence enhancement with excitation and emission maxima at 422 nm and 492 nm, respectively. A high two-photon cross section of 3.0 GM at 840 nm as well as excellent metal ion selectivity are reported. In vitro experiments on HEK 293 cell culture were carried out using two-photon microscopy to demonstrate the applicability of the novel sensor for zinc bioimaging. [ABSTRACT FROM AUTHOR]

Heavy metal pollution of soil, especially by lead (Pb) and cadmium (Cd), is a serious problem worldwide. The application of safe chelating agents, combined with the growing of tolerant trees, constitutes an approach for phytoremediation of heavy-metal-contaminated soil. This study aimed to determine whether the two safe chelators, tetrasodium glutamate diacetate (GLDA) and citric acid (CA), could improve the phytoremediation capacity of black locust (Robinia pseudoacacia L.) in a Pb–Cd-contaminated soil and to find the key factors affecting the biomass accumulation of stressed black locust. In Pb- and Cd-stressed black locust plants, medium- and high-concentration GLDA treatment inhibited the growth, chlorophyll synthesis and maximum photochemical efficiency (Fv / Fm), promoted the absorption of Pb and Cd ions and resulted in the shrinkage of chloroplasts and starch grains when compared with those in Pb- and Cd-stressed plants that were not treated with GLDA. The effects of CA on plant growth, ion absorption, chlorophyll content, chlorophyll fluorescence and organelle size were significantly weaker than those of GLDA. The effect of both agents on Cd absorption was greater than that on Pb absorption in all treatments. The levels of chlorophyll a and plant tissue Cd and rates of starch metabolism were identified as the key factors affecting plant biomass accumulation in GLDA and CA treatments. In the future, GLDA can be combined with functional bacteria and/or growth promoters to promote the growth of Pb- and Cd-stressed plants and to further improve the soil restoration efficiency following pollution by heavy metals. Application of CA combined with the growing of black locust plants has great potential for restoring the Cd-polluted soil. These findings also provide insights into the practical use of GLDA and CA in phytoremediation by R. pseudoacacia and the tolerant mechanisms of R. pseudoacacia to Pb–Cd-contaminated soil. [ABSTRACT FROM AUTHOR]

The reaction between [1,2,4,5]tetrazines with trans‐cyclooctene through the cycloaddition process has been described as a powerful tool in bioorthogonal processes. Specifically the diagnostic with fluorescent‐ and radio‐labelled [1,2,4,5]tetrazines and pre‐targeted trans‐cyclooctene modified‐antibody has been used by us for this purpose. Our previously developed 99mTc‐radiolabelled [1,2,4,5]tetrazine‐derivatives porting 6‐hydrazinonicotinyl‐chelator displayed some limitations related to its unappropriated biodisposal. Herein, we explored [1,2,4,5]tetrazines porting other 99mTc‐coordination‐moieties, 1,4,8,11‐tetrazacyclotetradecanyl and diethylenetriaminepentaacetyl, as potential hydrophilic functions. Some of the new modified [1,2,4,5]tetrazines were able to coordinate efficiently the radionuclide generating 99mTc‐counterparts that reacted with trans‐cyclooctene modified‐bevacizumab and recognized cells that overexpress vascular endothelial growth factor (VEGF). Additionally, the in vivo99mTc‐counterparts‐biodistributions were studied, on the desired organs, and they resulted dependent of lipophilicity. [ABSTRACT FROM AUTHOR]

Cobalt-containing alloys are useful for orthopedic applications due to their low volumetric wear rates, corrosion resistance, high mechanical strength, hardness, and fatigue resistance. Unfortunately, these prosthetics release significant levels of cobalt ions, which was only discovered after their widespread implantation into patients requiring hip replacements. These cobalt ions can result in local toxic effects--including peri-implant toxicity, aseptic loosening, and pseudotumor--as well as systemic toxic effects--including neurological, cardiovascular, and endocrine disorders. Failing metal-on-metal (MoM) implants usually necessitate painful, risky, and costly revision surgeries. To treat metallosis arising from failing MoM implants, a synovial fluid-mimicking chelator was designed to remove these metal ions. Hyaluronic acid (HA), the major chemical component of synovial fluid, was functionalized with British anti-Lewisite (BAL) to create a chelator (BAL-HA). BAL-HA effectively binds cobalt and rescues in vitro cell vitality (up to 370% of cells exposed to IC50 levels of cobalt) and enhances the rate of clearance of cobalt in vivo (t1/2 from 48 h to 6 h). A metallosis model was also created to investigate our therapy. Results demonstrate that BAL-HA chelator system is biocompatible and capable of capturing significant amounts of cobalt ions from the hip joint within 30 min, with no risk of kidney failure. This chelation therapy has the potential to mitigate cobalt toxicity from failing MoM implants through noninvasive injections into the joint. [ABSTRACT FROM AUTHOR]

The transition metal characteristics of iron allow it to play a fundamental role in several essential aspects of human life such as the transport of oxygen through hemoglobin or the transport of electrons in the mitochondrial respiratory chain coupled to the synthesis of ATP. However, an excess or deficiency of iron is related to certain pathologies. The maintenance of iron homeostasis is essential to avoid certain pathologies related to iron excess or deficiency. The existence of iron deposits in postmortem tissues of Parkinson's patients has been interpreted as evidence that iron plays a fundamental role in the degenerative process of the nigrostriatal system in this disease. The use of iron chelators has been successful in the treatment of diseases such as transfusion-dependent thalassemia and pantothenate kinase-associated neurodegeneration. However, a clinical study with the iron chelator deferiprone in patients with Parkinson's disease has not shown positive effects but rather worsened clinical symptoms. This suggests that iron may not play a role in the degenerative process of Parkinson's disease. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of these studies was to develop a nerve growth factor (NGF) radiometal-chelator conjugate to determine the biodistribution and brain uptake of NGF by positron emission tomography/computerized tomography (PET-CT). Procedures. Purified NGF from llama seminal plasma was conjugated with FITC, and the chelator NOTA or DFO. NGF conjugates were evaluated for bioactivity. NOTA- and DFO-conjugated NGF were radiolabeled with gallium-68 or zirconium-89 ([68 Ga]GaCl3, half-life = 68 min; [89Zr]Zr(oxalate)4, half-life = 3.3 days). [89Zr]Zr-NGF was evaluated for biodistribution (0.5, 1, or 24 h), PET imaging (60 min), and brain autoradiography in mice. Results: Cell-based in vitro assays confirmed that the NGF conjugates maintained NGF receptor-binding and biological activity. Zirconium-89 and gallium-68 radiolabeling showed a high efficiency; however, only[89Zr]Zr-NGF was stable in vitro. Biodistribution studies showed that, as with most small proteins < 70 kDa, [89Zr]Zr-NGF uptake was predominantly in the kidney and was cleared rapidly with almost complete elimination of NGF at 24 h. Dynamic PET imaging from 0–60 min showed a similar pattern to ex vivo biodistribution with some transient liver uptake. Interestingly, although absolute brain uptake was very low, at 24 h after treatment, cerebral cortex uptake was higher than any other brain area examined and blood. Conclusions: We conclude that conjugation of DFO to NGF through a thiourea linkage allows effective radiolabeling with zirconium-89 while maintaining NGF bioactivity. Following intravenous administration, the radiolabeled NGF targets non-neuronal tissues (e.g., kidney, liver), and although absolute brain uptake was very low, the brain uptake that was observed was restricted to the cortex. [ABSTRACT FROM AUTHOR]

In the present study, the aim is to synthesize and introduce the combination of methoxy amido xanthate MAX and then label it with 99mTc radionuclide as a novel diagnostic agent for single-photon computed tomography (SPECT) imaging. A chelator-designed ligand was synthesized from a blend of chloroacetamide and xanthate in certain proportions. After that MAX ligand labeling process was performed by directly milking 99mTc from the generator (99Mo / 99mTc). Thus, tin chloride was employed as a reducing agent, and the effect of parameters such as additives like ascorbic acid, changing the concentration of the cheating agent, and pH were evaluated to optimize the labeling conditions. The product was then identified by infrared spectroscopy (FTIR) and magnetic resonance imaging (NMR). Labeling of the complex at laboratory temperature was determined to be 93%. The new 99mTc-MAX radiopharmaceutical with a radionuclide and radiochemical purity of over 90% can be used as an encouraging diagnostic agent in clinics and preclinical studies, which will be addressed in future studies.

A method for the introduction of bifunctionalized 1,4,7,10-tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid (DOTA) into the bridging unit of peptide-based radiopharmaceuticals has been developed. The method is executed in the context of Fmoc-based solid-phase peptide synthesis (SPPS) using standard coupling reagents (HOAt, TBTU, DIPEA) and was optimized to maximize yields (>99% conversion) and suppress the formation of side products (

The world's arable land has been contaminated by heavy metals to a large extent, which has led to the decreasing availability of farmland. Thus, the remediation of heavy metal pollution deserves due attention, and phytoremediation is preferred. Hemp has been proposed as an ideal alternative crop for remediating heavy-metal-contaminated soil, owing to its well-developed roots, large biomass, and tolerance to heavy metals. Chelators can activate heavy metals to enhance plant absorption, but they may cause stress to plant growth. Therefore, it is very important to optimize the combination of chelator and plant (cultivar) for efficacious phytoremediation. The effects of different concentrations (2, 5, 10, 15, and 25 mmol·L−1) of the chelators disodium ethylene diamine tetra-acetate (EDTA) and citric acid (CA) on the seed germination and plant growth of hemp cultivars were investigated. Triple application of increasing concentrations of EDTA or CA two days apart gradually reduced the germination potential, germination rate, radicle length, and embryonic shoot length of hemp seed, although 2 mmol·L−1 of CA could even promote seed germination. Distinct varietal differences were found in the response of hemp to chelator stress. Under the scheme of four-time uses one week apart, both chelators caused a concentration-dependent linear decrease in the plant height, stem diameter, and biomass of hemp plants, but the growth inhibition due to CA was relatively milder. This could be partially explained by the change in tested physiological indices in hemp leaf. In conclusion, 2 mmol·L−1 of CA helped with seed germination and was almost nontoxic to plant growth; cultivar BM was more tolerant to the chelators than cultivar Y1. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) desorption rate is important in studying Cd leaching and phytoextraction in soils. This study estimated Cd desorption rates in soils and analyzed the sensitivity to soil properties under the influence of Cd complex sorption. The concentrations of Cd2+, Cd complex, and total Cd in 27 soils leached by DTPA and EDTA were analyzed, respectively. Kinetic models were used to fit desorption data to obtain the desorption rates of total Cd and Cd2+, respectively. The sensitivity of desorption rates to soil properties were analyzed. Results showed that, if omitting sorption of Cd complex, apparent desorption rates of total Cd varied between 1.9 and 9.2 × 10–2 min−1, and if considering sorption of Cd complex, desorption rates of Cd2+ varied between − 1.6 and 13.9 × 10–2 min−1. The relative differences between desorption rates of Cd2+ and apparent desorption rates varied between − 180% and 346%. Under maximum sorption level of Cd complex, there were about 62% DTPA experiments whose Cd2+ desorption rates were higher, whereas about 75% EDTA experiments whose Cd2+ desorption rates were lower, compared with the apparent desorption rates. The sensitivity of Cd2+ desorption rates were quite different from the sensitivity of apparent desorption rates to soil properties; moreover, the influence of soil properties on desorption rates became more nonlinear. This study demonstrated that sorbed Cd complex should be excluded from total Cd in investigating desorption rates of Cd2+ in soils leached by chelators. [ABSTRACT FROM AUTHOR]

Aim: This aim of this study was to compare the effects of different chelating agents [ethylenediaminetetraacetic acid (EDTA), glycolic acid (GA) and citric acid (CA)] on the push-out bond strength (POBS) of two calcium silicate-based silicate cements (CSC) (Biodentine and PD MTA White). Methodology: Dentin discs of 1 ± 0.2 mm thickness were taken from the middle root region of thirty-nine extracted mandibular premolar teeth and two holes (1 mm diameter) were drilled in each disc (n = 78 holes). The samples were then randomly divided into three groups (n = 26 holes) according to the final irrigation agents: Group 1: 20% CA, Group 2: 17% EDTA, Group 3: 10% GA. Then, two different materials were applied to the holes in each group (n = 13 holes): a: PD MTA White, b: Biodentine. POBS test was performed at a crosshead speed of 0.5 mm/min. The dentin discs were examined under stereomicroscope (25x) to assess the bond failure type. Data were analyzed using a two-way analysis of variance (ANOVA) and comparison of main effects was examined with the Bonferroni test, and multiple comparisons were analysed with the Tukey HSD test. The level of signifcance was 5%. Results: Biodentine showed significantly higher POBS than PD MTA White (p < 0.05). There was no significant difference between the final irrigation agents (p > 0.05). CA -- Biodentine group showed substantially higher POBS than EDTA -- PD MTA White, CA -- PD MTA White, and GA -- Biodentine groups (p < 0.05). Conclusion: While CA increased the POBS of Biodentine significantly, the POBS of PD MTA White was not affected by the final irrigation agents. [ABSTRACT FROM AUTHOR]

We exploited bacterial infection assays using the fruit fly Drosophila melanogaster to identify anti-infective compounds that abrogate the pathological consequences in the infected hosts. Here, we demonstrated that a pyridine-3-N-sulfonylpiperidine derivative (4a) protects Drosophila from the acute infections caused by bacterial pathogens including Pseudomonas aeruginosa. 4a did not inhibit the growth of P. aeruginosa in vitro, but inhibited the production of secreted toxins such as pyocyanin and hydrogen cyanide, while enhancing the production of pyoverdine and pyochelin, indicative of iron deprivation. Based on its catechol moiety, 4a displayed iron-chelating activity in vitro toward both iron (II) and iron (III), more efficiently than the approved iron-chelating drugs such as deferoxamine and deferiprone, concomitant with more potent antibacterial efficacy in Drosophila infections and unique transcriptome profile. Taken together, these results delineate a Drosophila–based strategy to screen for antipathogenic compounds, which interfere with iron uptake crucial for bacterial virulence and survival in host tissues.

Omadine or N-hydroxypyridine-2-thione and its metal complexes are widely used in medicine and show bactericidal, fungicidal, anticancer, and photochemical activity. The redox activity of omadine complexes with iron, copper, and zinc on lipid peroxidation under light and dark conditions has been investigated. The monitoring of the oxidation of linoleic acid micelles, resembling a model of lipid membrane, was carried out using nuclear magnetic resonance (1H-NMR). It has been shown that the omadine–zinc complex can induce the oxidation of linoleic acid under light irradiation, whereas the complexes with iron and copper are photochemically stable. All the chelating complexes of omadine appear to be redox-inactive in the presence of hydrogen peroxide under dark conditions. These findings suggest that omadine can demonstrate antioxidant behavior in processes involving reactive oxygen species generation induced by transition metals (Fenton and photo-Fenton reactions). However, the omadine complex with zinc, which is widely used in shampoos and ointments, is photochemically active and may cause oxidative cell membrane damage when exposed to light, with possible implications to health. [ABSTRACT FROM AUTHOR]

Bone and soft tissue infections are potentially life-threatening and require immediate and intensive treatment. However, there is still no single diagnostic method that can reliably confirm or rule out such conditions. Imaging with radiopharmaceuticals (i.e., scintigraphy) is a powerful diagnostic tool in the management of patients with infectious or inflammatory diseases. In this work, a new and efficient way to modify the thiazole ring of the cefepime molecule has been proposed and experimentally verified. The developed organic synthesis routes allow for the coupling of the appropriate complexing ligand of the gallium-68 radionuclide with cefepime. The new NODAGA-Glu-CFM conjugate was radiolabeled with gallium-68 with a high yield and showed full stability in human serum. In addition, the [68Ga]Ga-NODAGA-Glu-CFM radioconjugate was hydrophilic and positively charged. Therefore, on the basis of these results, the [68Ga]Ga-NODAGA-Glu-CFM radioconjugate might be considered as a new promising radioconjugate for the diagnosis of bacterial infections. [ABSTRACT FROM AUTHOR]

Metal chelators are used for various industrial and medical purposes based on their physicochemical properties and biological activities. In biological systems, copper ions bind to certain enzymes as cofactors to confer catalytic activity or bind to specific proteins for safe storage and transport. However, unbound free copper ions can catalyze the production of reactive oxygen species (ROS), causing oxidative stress and cell death. The present study aims to identify amino acids with copper chelation activities that might mitigate oxidative stress and toxicity in skin cells exposed to copper ions. A total of 20 free amino acids and 20 amidated amino acids were compared for their copper chelation activities in vitro and the cytoprotective effects in cultured HaCaT keratinocytes exposed to CuSO4. Among the free amino acids, cysteine showed the highest copper chelation activity, followed by histidine and glutamic acid. Among the amidated amino acids, cysteinamide showed the highest copper chelation activity, followed by histidinamide and aspartic acid. CuSO4 (0.4–1.0 mM) caused cell death in a concentration-dependent manner. Among the free and amidated amino acids (1.0 mM), only histidine and histidinamide prevented the HaCaT cell death induced by CuSO4 (1.0 mM). Cysteine and cysteinamide had no cytoprotective effects despite their potent copper-chelating activities. EDTA and GHK-Cu, which were used as reference compounds, had no cytoprotective effects either. Histidine and histidinamide suppressed the CuSO4-induced ROS production, glutathione oxidation, lipid peroxidation, and protein carbonylation in HaCaT cells, whereas cysteine and cysteinamide had no such effects. Bovine serum albumin (BSA) showed copper-chelating activity at 0.5–1.0 mM (34–68 mg mL−1). Histidine, histidinamide, and BSA at 0.5–1.0 mM enhanced the viability of cells exposed to CuCl2 or CuSO4 (0.5 mM or 1.0 mM) whereas cysteine and cysteinamide had no such effects. The results of this study suggest that histidine and histidinamide have more advantageous properties than cysteine and cysteinamide in terms of alleviating copper ion-induced toxic effects in the skin. [ABSTRACT FROM AUTHOR]

Copper alloys objects can deteriorate their conservation state through irreversible corrosion. Since in the cultural heritage field every artefact is unique and any loss irreplaceable, solutions for conservation are needed. Hence, there is the necessity to stop the corrosion process with a suitable cleaning and conservation process to avoid further degradation processes without changing its morphological aspect. Chelating solutions are commonly used in chemical cleaning, mainly sodium salts of ethylenediaminetetraacetic acid (EDTA). However, it is resistant to water purification procedures and is not biodegradable. The goal of this study was to see if applying an ecologically friendly chelating agent as an alternative to EDTA cleaning procedures for cultural heritage was suitable. In this study were chosen six natural-based chelators that could be a new green non-toxic alternative to EDTA in corrosion-inhibiting properties. They were tested for cleaning copper artefacts exposed to atmospheric environment in polluted areas. The study considered four amino acids, a glucoheptonate (CSA) and an industrial green chelator (GLDA). The effectiveness was tested on corrosion copper compounds and on laboratory corroded copper sheets. Finally, the cleaning efficacy was tested on four Roman coins and a modern copper painting. To define the cleaning efficacy, surface analytical investigations have been carried out by means ICP-OES, UV-VIS, µ-Raman, spectro-colorimetry, XRD and FTIR. Among the amino acids, alanine was the most effective, showing an unaltered noble patina and a good effective copper recovery from corrosion patinas. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the possibility of using the colistin disk chelator application (CDCA) method as simple and available screening tool for detection of mcr-1-mediated resistance to polymyxins in Enterobacterales. Materials and Methods. A total of 47 colistin-resistant Enterobacterales isolates obtained in 2014–2020 within multicenter MARATHON study were included in the experiment. Colistin susceptibility testing was performed using Mueller–Hinton broth microdilution method according to ISO 20776-1:2006. Interpretation of the results was performed according to EUCAST v.12.0 clinical breakpoints. MCR-genes were detected by multiplex real-time PCR. Phenotypic screening for mcr-expression was performed on Mueller–Hinton agar by application of dipicolinic acid in concentration of 1,000 mcg/disk in 10 µL volume per disk and 0.5 M solution of EDTA in 5 µL volume per disk. Chelating effect was registered by differences in zone of growth inhibition around colistin disks with and without chelator. Measurements were performed with the help of caliper in millimeters. Statistical data processing was carried out in accordance with guidelines for statistical analysis in medical researches using MS-Excel tool. Results. In 25 of 47 included in the experiment enterobacteria isolates mcr-genes were detected by molecular method. MCR-detection by CDCA method identified the average difference value of the zones of growth inhibition for colistin and its combination with EDTA and DPA as 4.1 mm and 3.7 mm respectively for mcr-positive isolates and 1.7 mm and 1.2 mm respectively for mcr-negative isolates. Statistical analysis estimated that a difference of ≥ 3 mm in zone of growth inhibition for combination of colistin with one of the chelating agents when compared to colistin only allows us to conclude that a studied isolated carries mcr-1-mediated resistance to polymyxins. In addition, sensitivity of the test was 96% and specificity was 91% if DPA is used, while EDTA showed only 88% sensitivity and 77% specificity. Conclusions. Proposed method appears as available technique for phenotypic screening of the Enterobacterales order for mcr-1-mediated resistance to polymyxins for practical laboratories in present conditions. The use of DPA is preferred because of better specificity and sensitivity rates.

Bacteria have developed a tendency to form biofilms, where bacteria live in organized structures embedded in a self-produced matrix of DNA, proteins, and polysaccharides. Additionally, bacteria need iron(III) as an essential nutrient for bacterial growth and secrete siderophore groups that sequester it from the environment. To design a molecule able both to inhibit the bacteria and to sequester iron, we developed two hydroxamate-based peptides derived from an analog (WMR-4), previously developed in our lab, of the antimicrobial peptide myxinidin. In detail, we proposed a combination of WMR-4 with the hydroxamic acid resulting in the peptides WMR-7 and WMR-16 which differ for the length of the linker between the antimicrobial moiety and the siderophore. Both peptides were characterized through a set of different biophysical experiments to investigate their ability to sequester Fe3+. The peptide‑iron(III) complexes were studied through the UV–visible spectroscopy in organic solvent to eliminate water competition, and in acidic water to avoid iron precipitation. The complexes were also characterized by performing electrochemistry, circular dichroism and NMR spectroscopy experiments. In addition, we demonstrated the ability of peptide‑iron(III) complexes to inhibit the biofilm of Pseudomonas aeruginosa and to have an impact on the cell motility. This metal-based approach consisting in a hydroxamic acid conjugation represents a promising strategy to enhance the antibiofilm activity of antimicrobial peptides against one of most dangerous bacteria such as Pseudomonas aeruginosa. Representation of hydroxamate-based peptides activity on Pseudomonas aeruginosa biofilm. [Display omitted] • hydroxamate unit, chelator, iron (III), antimicrobial peptides,siderophore, pseudomonas aeruginosa , biofilm , siderophore. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) utilizes visible light to activate the cytotoxic effects of photosensitizing drugs. PDT protocols require optimization to overcome treatment resistance and induce a beneficial anti-tumor immune response. The aim of this study was to examine the possibility to suppress the resistance of esophageal cell lines to aminolevulinic acid (ALA)-PDT by administration of iron chelators to induce sufficient cell cytotoxicity under pathophysiologically relevant conditions, mimicking the advanced stages of cancer. Effects of ALA-PDT in combination with iron chelators were compared in three esophageal cell lines in conventional monolayers and in 3 D cultures based on collagen type I. Modified colony assay and fluorescence-based live cell imaging, respectively were applied. The latter was used also to test the capability of pre-polarized macrophages to interact with cancer cells subjected to ALA-PDT with or without iron chelators. Iron chelators were effective in the enhancement of ALA-PDT in all cell lines under both culture conditions. Fluorescence evaluation of cell viability in 3 D cultures indicated the contribution of apoptotic cell death after ALA-PDT, both with and without iron chelators. Engulfment of remnants of dead cancer cells by macrophages in 2 D cultures was indicated, however, the interaction between macrophages and cancer cells in 3 D cultures subjected to ALA-PDT with or without iron chelators was not present. The potential of iron chelators to enhance ALA-PDT was maintained in 3 D collagen matrices. Although PDT dose (ALA concentration, light exposure time) required modification in a cell line-dependent manner to achieve a comparable effect of PDT alone in conventional monolayers and in collagen matrices, the potential of iron chelators to suppress the resistance of esophageal cells to ALA-PDT was not influenced by a fibrillar collagen matrix. [ABSTRACT FROM AUTHOR]

The antiviral drugs tecovirimat, brincidofovir, and cidofovir are considered for mpox (monkeypox) treatment despite a lack of clinical evidence. Moreover, their use is affected by toxic side‐effects (brincidofovir, cidofovir), limited availability (tecovirimat), and potentially by resistance formation. Hence, additional, readily available drugs are needed. Here, therapeutic concentrations of nitroxoline, a hydroxyquinoline antibiotic with a favourable safety profile in humans, inhibited the replication of 12 mpox virus isolates from the current outbreak in primary cultures of human keratinocytes and fibroblasts and a skin explant model by interference with host cell signalling. Tecovirimat, but not nitroxoline, treatment resulted in rapid resistance development. Nitroxoline remained effective against the tecovirimat‐resistant strain and increased the anti‐mpox virus activity of tecovirimat and brincidofovir. Moreover, nitroxoline inhibited bacterial and viral pathogens that are often co‐transmitted with mpox. In conclusion, nitroxoline is a repurposing candidate for the treatment of mpox due to both antiviral and antimicrobial activity. [ABSTRACT FROM AUTHOR]

Background and Purpose: Traumatic brain injury (TBI) remains a leading cause of mortality and morbidity in young adults. The role of iron in potentiating neurodegeneration following TBI has gained recent interest as iron deposition has been detected in the injured brain in the weeks to months post‐TBI, in both the preclinical and clinical setting. A failure in iron homeostasis can lead to oxidative stress, inflammation and excitotoxicity; and whether this is a cause or consequence of the long‐term effects of TBI remains unknown. Experimental Approach: We investigated the role of iron and the effect of therapeutic intervention using a brain‐permeable iron chelator, deferiprone, in a controlled cortical impact mouse model of TBI. An extensive assessment of cognitive, motor and anxiety/depressive outcome measures were examined, and neuropathological and biochemical changes, over a 3‐month period post‐TBI. Key Results: Lesion volume was significantly reduced at 3 months, which was preceded by a reduction in astrogliosis, microglia/macrophages and preservation of neurons in the injured brain at 2 weeks and/or 1 month post‐TBI in mice receiving oral deferiprone. Deferiprone treatment showed significant improvements in neurological severity scores, locomotor/gait performance and cognitive function, and attenuated anxiety‐like symptoms post‐TBI. Deferiprone reduced iron levels, lipid peroxidation/oxidative stress and altered expression of neurotrophins in the injured brain over this period. Conclusion and Implications: Our findings support a detrimental role of iron in the injured brain and suggest that deferiprone (or similar iron chelators) may be promising therapeutic approaches to improve survival, functional outcomes and quality of life following TBI. [ABSTRACT FROM AUTHOR]

Phytic acid (PA), extracted from oilseeds, legumes, cereals, nuts, and pollen by acid solutions under heating and/or stirring and then purified, has shown beneficial health and physiological effects due to its pronounced antioxidant activity and ability to chelate Fe3+ ions. Publications on PA have increased, especially the ones reporting its effect on disease prevention and treatment. Moreover, recent studies have suggested the PA efficacy as a foodborne pathogens inhibitor. Therefore, due to its countless proven properties, phytic acid has gained greater attention than its common classification as just an antinutrient. Past and current studies have been reviewed to provide an overview on PA structure, sources, biosynthesis, extraction, purification, and applications. [ABSTRACT FROM AUTHOR]

Plants typically interact with a variety of microorganisms, including bacteria, mycorrhizal fungi, and other organisms, in their above- and below-ground parts. In the biosphere, the interactions of plants with diverse microbes enable them to acquire a wide range of symbiotic advantages, resulting in enhanced plant growth and development and stress tolerance to toxic metals (TMs). Recent studies have shown that certain microorganisms can reduce the accumulation of TMs in plants through various mechanisms and can reduce the bioavailability of TMs in soil. However, relevant progress is lacking in summarization. This review mechanistically summarizes the common mediating pathways, detoxification strategies, and homeostatic mechanisms based on the research progress of the joint prevention and control of TMs by arbuscular mycorrhizal fungi (AMF)-plant and Rhizobium-plant interactions. Given the importance of tripartite mutualism in the plant-microbe system, it is necessary to further explore key signaling molecules to understand the role of plant-microbe mutualism in improving plant tolerance under heavy metal stress in the contaminated soil environments. It is hoped that our findings will be useful in studying plant stress tolerance under a broad range of environmental conditions and will help in developing new technologies for ensuring crop health and performance in future. [ABSTRACT FROM AUTHOR]